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Structure paper

タイトル	eIF2B-catalyzed nucleotide exchange and phosphoregulation by the integrated stress response.
ジャーナル・号・ページ	Science, Vol. 364, Issue 6439, Page 491-495, Year 2019
掲載日	2019年5月3日
著者	Lillian R Kenner / Aditya A Anand / Henry C Nguyen / Alexander G Myasnikov / Carolin J Klose / Lea A McGeever / Jordan C Tsai / Lakshmi E Miller-Vedam / Peter Walter / Adam Frost /
PubMed 要旨	The integrated stress response (ISR) tunes the rate of protein synthesis. Control is exerted by phosphorylation of the general translation initiation factor eIF2. eIF2 is a guanosine triphosphatase ...The integrated stress response (ISR) tunes the rate of protein synthesis. Control is exerted by phosphorylation of the general translation initiation factor eIF2. eIF2 is a guanosine triphosphatase that becomes activated by eIF2B, a two-fold symmetric and heterodecameric complex that functions as eIF2's dedicated nucleotide exchange factor. Phosphorylation converts eIF2 from a substrate into an inhibitor of eIF2B. We report cryo-electron microscopy structures of eIF2 bound to eIF2B in the dephosphorylated state. The structures reveal that the eIF2B decamer is a static platform upon which one or two flexible eIF2 trimers bind and align with eIF2B's bipartite catalytic centers to catalyze nucleotide exchange. Phosphorylation refolds eIF2α, allowing it to contact eIF2B at a different interface and, we surmise, thereby sequestering it into a nonproductive complex.
リンク	Science / PubMed:31048491 / PubMed Central
手法	EM (単粒子)
解像度	3.03 - 3.21 Å
構造データ	0649 6o81 EMDB-0649, PDB-6o81: Electron cryo-microscopy of the eukaryotic translation initiation factor 2B bound to translation initiation factor 2 from Homo sapiens 手法: EM (単粒子) / 解像度: 3.21 Å 0651 6o85 EMDB-0651, PDB-6o85: Electron cryo-microscopy of the eukaryotic translation initiation factor 2B bound to eukaryotic translation initiation factor 2 from Homo sapiens 手法: EM (単粒子) / 解像度: 3.03 Å 0664 6o9z EMDB-0664, PDB-6o9z: Electron cryo-microscopy of the eukaryotic translation initiation factor 2B bound to eukaryotic translation initiation factor 2 from Homo sapiens 手法: EM (単粒子) / 解像度: 3.03 Å
化合物	ChemComp-C7B: 2-(4-chloranylphenoxy)-~{N}-[4-[2-(4-chloranylphenoxy)ethanoylamino]cyclohexyl]ethanamide / N-[4α-[[(4-クロロフェノキシ)アセチル]アミノ]シクロヘキサン-1β-イル]-2-(4-クロロフェニルオキシ(以下略) / 阻害剤*YM
由来	homo sapiens (ヒト)
キーワード	TRANSLATION / Translation initiation / eukaryotic translation initiation factor 2B / eukaryotic translation initiation factor 2